Francais | English | Espanõl

Vitamin D

From Wikipedia, the free encyclopedia

Jump to: navigation, search

Image:Cholecalciferol.png Image:Ergocalciferol.png

Vitamin D refers to a group of fat-soluble prohormones as well as to the metabolites and analogues of these substances. Two major forms of vitamin D are D2 (or ergocalciferol) and D3 or cholecalciferol.<ref name = FactD>Dietary Supplement Fact Sheet: Vitamin D. National Institutes of Health. Retrieved on 2006-06-10.</ref> Vitamin D3 is produced in skin exposed to sunlight, specifically ultraviolet B radiation. Very few foods are naturally rich in vitamin D, and most vitamin D intake is in the form of fortified products including milk and cereal grains.<ref name = FactD/>

Vitamin D plays an important role in the maintenance of several organ systems.<ref name= Merck>Vitamin D The Merck Manual of Diagnosis and Therapy. Last modified November 2005</ref>

Vitamin D deficiency can result from; inadequate intake coupled with inadequate sunlight exposure, disorders that limit its absorption, conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders, or, rarely, by a number of hereditary disorders.<ref name= Merck/> Deficiency results in impaired bone mineralization, and leads to bone softening diseases, rickets in children and osteomalacia in adults, and possibly contributes to osteoporosis.<ref name= Merck/>

Contents

[edit] Forms

Several forms of vitamin D have been described. The the two major forms involved in humans are D2 or ergocalciferol, and D3 or cholecalciferol.

Chemically, the various forms of vitamin D are secosteroids; i.e. broken-open steroids.<ref name= River>About Vitamin D Including Sections: History, Nutrition, Chemistry, Biochemistry, and Diseases. University of California Riverside</ref>.

Ergocalciferol (vitamin D2) is derived from fungal and plant sources, and is not produced by the human body. Vitamin D3, also known as cholecalciferol, is derived from animal sources and is made in the skin when 7-dehydrocholesterol reacts with UVB ultraviolet light<ref name=PDR>Vitamin D The Physicians Desk Reference. 2006 Thompson Healthcare.</ref> with wavelengths 290 to 315 nm. These wavelengths are present in sunlight at sea level when the sun is more than 45 degrees above the horizon, or when the UV index is greater than 3.<ref>Fun with UVB Includes calculations and measurements of UVB levels at various angles of solar rays.</ref> Typically, 10,000  IU (250 micrograms) can be made in the skin only after one minimal erythemal dose of exposure, or until the skin just begins to turn pink. An equilibrium is achieved in the skin when longer exposure to UVB simply degrades the product as fast as it is generated.<ref name = FactD/>

The structural difference between vitamin D2 and vitamin D3 is in their side chains. The side chain of D2 contains a double bond between carbons 22 and 23, and a methyl group on carbon 24. In most mammals including humans, D3 is more effective than D2 at increasing levels of vitamin D hormone in the circulation.<ref>Laura A. G. Armas, Bruce W. Hollis and Robert P. Heaney (2004). "Full Text Vitamin D2 Is Much Less Effective than Vitamin D3 in Humans". The Journal of Clinical Endocrinology & Metabolism 89 (11): 5387–5391.</ref> In rats, D2 is more effective than D3.<ref> Coates, M. E. (1968). "Requirements of different species for vitamins". Proceedings of the Nutrition Society 27 (2): 143–148. PMID 5755261 DOI:10.1079/PNS19680039.</ref> However both vitamin D2 and D3 are used for nutritional supplementation. Pharmaceutical forms of vitamin D include calcitriol (1alpha, 25-dihydroxycholecalciferol), doxercalciferol and calcipotriene.<ref name=PDR/>

[edit] Biochemistry

Vitamin D is a prohormone, that is, it has no hormone activity itself, but is converted to a molecule which does, through a tightly regulated synthesis mechanism.

[edit] Synthesis mechanism (form 3)

1. Vitamin D3 is synthesized from 7-dehydrocholesterol, a derivative of cholesterol, which is then photolyzed by ultraviolet light in 6-electron conrotatory electrocyclic reaction. The product is pre-vitamin D3. Image:Reaction-Dehydrocholesterol-PrevitaminD3.png
2. Pre-vitamin D3 then spontaneously isomerizes to Vitamin D3 in a antarafacial hydride [1,7]Sigmatropic shift. Image:Reaction-PrevitaminD3-VitaminD3.png
3. Whether it is made in the skin or ingested, vitamin D3 (cholecalciferol) is then hydroxylated in the liver to 25-hydroxycholecalciferol (25(OH)D3 or calcidiol) and stored until it is needed. 25-hydroxycholecalciferol is further hydroxylated in the kidneys to into two dihydroxylated metabolites, the main biologically active hormone 1,25-dihydroxycholecalciferol (1,25(OH)2D3 or calcitriol) and 24R,25(OH)2D3. This conversion occurs in a tightly regulated fashion. Calcitriol is represented below right (hydroxylated Carbon 1 is on the lower ring at right, hydroxylated Carbon 25 is at the upper right end). Image:Reaction-VitaminiD3-Calcitriol.png

[edit] Mechanism of action

Following synthesis the active form of Vitamin D3 (calcitriol or 1,25(OH)2D3) it is released into the circulation, and through its association with the carrier protein plasma vitamin D binding protein (DBP), is transported to various target organs.<ref name= River/>

The hormonally active form of vitamin D3, calcitriol (or 1,25-(OH)2D3) mediates its biological effects by binding to vitamin D receptors (VDR) which are principally located in the nuclei of target cells.<ref name= River/>. The VDR belongs to the superfamily of steroid/thyroid hormone receptors, and becomes capable of influencing cellular processes only after it has interacted with its ligand, calcitriol. The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins (such as TRPV6 and calbindin), which are involved in calcium absorption in the intestine.

Vitamin D receptors are expressed by cells in most organs in the body, including the brain, heart, skin, gonads, prostate, and breast. VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood (with the assistance of parathyroid hormone and calcitonin) and to the maintenance bone content.<ref name= Sun>Holick MF (2004). "Full Text Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease". American Journal of Clinical Nutrition 80 (6): 1678S-1688S.</ref>

Vitamin D receptors are also constitutively expressed in monocytes and induced upon activation of T and B lymphocytes, and the VDR is known to be involved in cell proliferation, differentiation, and immunomodulation.<ref name=PDR/>

Molecular modeling calculations suggest that, at least in theory, the active form of vitamin D might also have an affinity for several steroid receptors, including glucocorticoid and thyroid receptors.<ref name="FDA"> Marshall T.G. (2006) “Molecular genomics offers new insight into the exact mechanism of action of common drugs - ARBs, Statins, and Corticosteroids.” FDA CDER Visiting Professor presentation. FDA Biosciences Library, Accession QH447.M27 2006. Slide presentation: http://autoimmunityresearch.org/fda_visiting-professor_7mar06_144dpi.pdf</ref>

[edit] Nutrition

A blood calcidiol (25-hydroxy-vitamin D) level is the accepted way to determine vitamin D nutritional status. The optimal level of serum 25-hydroxyvitamin D remains a point for debate among medical scientists. One recent consensus concluded that for optimal prevention of osteoporotic fracture the blood calcidiol concentration should be higher than 30 ng/mL (US units), which is equal to 75 nmol/L (System International units).<ref name = FactD/>

The U.S. Dietary Reference Intake for Adequate Intake (AI) of vitamin D for infants, children and men and women aged 19-50 is 5 micrograms/day (200 units/day).<ref>In scientific literature, vitamin D dosage in usually reported in micrograms, whereas food and supplement regulations typically require dosages on labels to be in International Units (IU).</ref> Adequate intake increases to 10 micrograms/day (400 units/day) for men and women 51-70 and to 15 micrograms/day (600 units/day) past age 70.<ref name = FactD/>

[edit] In food

At higher latitudes, total vitamin D input from sunlight is usually insufficient, especially in the winter. To minimize risk of low vitamin D concentrations, foods such as milk are often fortified with vitamin D2 and/or vitamin D3, typically providing 100 IU per glass.<ref name = FactD/> Fortified foods are the major dietary sources of vitamin D. Prior to the fortification of milk products with vitamin D rickets, was a major public health problem. Since the 1930s, milk has been fortified with 10 micrograms (400 IU) of vitamin D per quart, in the United States, where rickets is now uncommon.<ref name= Sun/>

One cup of vitamin D fortified milk supplies about one-fourth of the official estimated adequate intake of vitamin for adults older than age 50 years. Although milk is often fortified with vitamin D, dairy products made from milk (cheese, yogurt, ice cream, and so forth) are generally not. Only a few foods naturally contain significant amounts of vitamin D, including:<ref name = FactD/>

The U.S. Dietary Reference Intake Tolerable Upper Intake Level (UL) of vitamin D for childern and adults is 50 micrograms/day (2000 IU/day). For infants (birth to 12 months) the UL is 25 micrograms/day (1000 IU/day).

[edit] Diseases caused by deficiency

The isolation of vitamin D and its functional role in rickets was determined by Edward Mellanby between 1918–1920. The 1928 Nobel Prize was awarded to Adolf Windaus, who discovered the steroid, 7-dehydrocholesterol, the precursor of vitamin D.

Vitamin D deficiency is known to cause several bone diseases<ref>Grant WB, Holick MF (2005). "Benefits and requirements of vitamin D for optimal health: a review". Altern Med Rev 10 (2): 94-111. PMID 15989379.</ref> including:

Vitamin D malnutrition may also be linked to an increased susceptibility to several chronic diseases such as tuberculosis, cancer, chronic pain, several autoimmune diseases, high blood pressure, depression, and seasonal affective disorder.<ref name= Sun/>

[edit] Groups with greater deficiency risk

Vitamin D requirements increase with age and the ability of skin to convert 7-dehydrocholesterol to pre-vitamin D3 decreases. In addition the ability of the kidneys to convert calcidiol to its active form, also decreases with age, prompting the need for increased vitamin D supplementation, in elderly individuals.

The Canadian and American Pediatric Associations advise vitamin D supplementation from birth onwards, with 200 IU/day (5 mcg/d) in the south up to 800 IU/day in the north.<ref name = FactD/> . While infant formula is generally fortified with vitamin D, breast milk does not contain significant levels of vitamin D, and parents are usually advised to avoid exposing babies to prolonged exposure to sunlight. Therefore, infants who are exclusively breastfed require vitamin D supplements. Liquid "drops" of vitamin D, as a single nutrient or combined with other vitamins, are available in water based or oil-based preparations ("Baby Drops" in North America, or "Vigantol oil" in Europe).

Obese individuals may have lower levels of the circulating form of vitamin D, probably due to reduced bioavailability, and are at higher risk of deficiency. Patients with chronic liver disease or intestinal malabsorption may require larger doses of vitamin D (up to 40,000 IU or 1 mg (1000 micrograms) daily). To maintain blood levels of calcium, therapeutic vitamin D doses are sometimes administered (up to 100,000 IU or 2.5 mg daily) to patients who have had their parathyroid glands removed (most commonly renal dialysis patients who have had tertiary hyperparathyroidism, but also patients with primary hyperparathyroidism) or who suffer with hypoparathyroidism.<ref>Holick MF (2005). "Full Text The vitamin D epidemic and its health consequences". J Nutr 135 (11): 2739S-48S.</ref>

Those who avoid or are not exposed to midday sunshine may also require vitamin D supplements. Although a few minutes of exposure for light-skinned individuals may be all that is required, the dermatology community contends that even a few minutes of unprotected ultraviolet exposure a day increases the risk of skin cancer and causes photoaging of the skin. The use of sunscreen with an sun protection factor (SPF) of 8 inhibits more than 95% of vitamin D production in the skin.<ref name= Sun/> To avoid vitamin D deficiency dermatologists recommend supplementation along with sunscreen use.

Recent studies showed that, following the successful "Slip-Slop-Slap" health campaign encouraging Australians to cover up when exposed to sunlight to prevent skin cancer, an increased number of Australians and New Zealanders became vitamin D deficient.<ref>Caryl A Nowson and Claire Margerison (2002). "Vitamin D intake and vitamin D status of Australians". The Medical Journal of Australia 177 (3): 149–152. PMID 12149085.</ref> Ironically, there are indications that vitamin D deficiency may lead to skin cancer.<ref>Grant WB (2002). "An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation". Cancer 94 (6): 1867-75. PMID 11920550.</ref>

At higher latitudes (above 30°), the decreased angle of the sun's rays, reduced daylight hours in winter, and protective clothing worn to guard against cold weather, diminish absorption of sunlight and the production of vitamin D. Because melanin acts like a sun-block, prolonging the time required to generate vitamin D, dark-skinned individuals, in particular, may require extra vitamin D to avoid deficiency. At latitudes below 30° where sunlight and day-length are more consistent, and vitamin D supplementation may not be required.<ref>Fun with UVB Includes calculations and measurements of UVB levels at various angles of solar rays.</ref> The reduced pigmentation of light-skinned individuals tends to allow more sunlight to be absorbed even at higher latitudes, thereby reducing the risk of vitamin D deficiency.<ref>Heaney RP (2004). "Full Text Functional indices of vitamin D status and ramifications of vitamin D deficiency". Am J Clin Nutr 80 (6 Suppl): 1706S-9S.</ref>

[edit] Overdose

Vitamin D stored in the human body as calcidiol (25-hydroxy-vitamin D) has a large volume of distribution and a long half-life (about 20 to 29 days).<ref name= PDR/> However, the synthesis of bioactive vitamin D hormone, from clacidiol, is tightly regulated and vitamin D toxicity usually occurs only if excessive doses (prescription or megavitamin) are taken.<ref name="homestead">RODENTICIDES, source: Journal of Veterinary Medicine, archives, vol. 27, May, 1998. IPM Of Alaska, Solving Pest Problems Sensibly. Retrieved on 2006-07-07.</ref> Although normal food and pill vitamin D concentration levels are too low to be toxic, because of the high vitamin A content in cod-liver oil (if taken in multiples of the normal dose) it is possible to reach poisonous levels. Vitamin D overdose has been also been recorded due to manufacturing and industrial accidents.

The exact long-term safe dose of vitamin D is not entirely known, but dosages up to 60 micrograms (2,400 IU)/day in healthy individuals (10x the RDA) are believed to be safe.<ref name= PDR/> Vitamin D concentrations of 1000 μg (40,000 IU) per day produce toxicity within 1 to 4 months in infants. In adults, sustained intake of 2500 μg (100,000 IU) per day can produce toxicity within a few months, and, if taken for years, as little as 50 to 75 μg (2000 to 3000 IU) per day can produce toxicity.<ref name= Merck/>

Serum levels of calcidiol (25-hydroxy-vitamin D) are typically used to diagnose vitamin D toxicity and may be as much as 15-fold greater then normal. Levels of bioactive vitamin hormone (1,25(OH2)D or calcitriol), are usually normal.<ref name= Merck/>

The symptoms of vitamin D toxicity or (Hypervitaminosis D) are a result of hypercalcemia (an elevated level of calcium in the blood) caused by increased intestinal calcium absorption. Gastrointestinal symptoms of vitamin D toxicity can develop including anorexia, nausea, and vomiting. These symptoms are often followed by polyuria (excessive production of urine), polydipsia (increased thirst), weakness, nervousness, pruritus (itch), and eventually renal failure. Other signals of kidney disease including elevated protein levels in the urine, urinary casts, and a build up of wastes in the blood stream can also develop.<ref name= Merck/> In one study, hypercalciuria and bone loss occurred at serum concentrations of 25D above 50 ng/mL in patients supplementing with up to 3600 IU/day of D3.<ref>Adams JS, Lee G (1997). "Gains in bone mineral density with resolution of vitamin D intoxication". Ann Intern Med 127 (3): 203-206. PMID 9245225.</ref> Another study showed elevated risk of ischaemic heart disease when 25D was above 89 ng/mL.<ref>Rajasree S, Rajpal K, Kartha CC, Sarma PS, Kutty VR, Iyer CS, Girija G (2001). "Full Text Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease". Eur J Epidemiol 17 (6): 567-71. PMID 11949730.</ref>

Vitamin D toxicity is treated by discontinuing vitamin D supplementation, and restricting calcium intake. If the toxicity is severe blood calcium levels can be further reduced with corticosteroids or bisphosphonates. In some cases kidney damage may be irreversible.<ref name= Merck/>

In the United States in 2004, overdose exposure of vitamin D was reported by 284 individuals, leading to 1 “major” outcome and 0 deaths.<ref>2004 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System.</ref>

[edit] Role in immunoregulation

The hormonally active form of vitamin D3, calcitriol (or 1,25-(OH)2D3) mediates immunological effects by binding to nuclear vitamin D receptors (VDR) which are present in most immune cell types including both innate and adaptive immune cells. The VDR is expressed constitutively in monocytes and in activated macrophages, dendritic cells, NK cells, T and B cells. In line with this observation, activation of the VDR has been identified as eliciting potent anti-proliferative, pro-differentiative, and immunomodulatory functions including both immune-enhancing and immunosuppressive effects.<ref name= Endo>Nagpal, Sunil, Songqing Naand Radhakrishnan Rathnachalam (2005) Noncalcemic Actions of Vitamin D Receptor Ligands Full Text html Endocrine Reviews 26 (5): 662-687.</ref>

Effects of VDR-ligands, such as calcitriol, on T-cells include; suppression of effector T cell activation and induction of regulatory T cells, as well as effects on cytokine secretion patterns.<ref>Yee YK, Chintalacharuvu SR, Lu J, Nagpal S. (2005). "Vitamin D receptor modulators for inflammation and cancer.". Mini Rev Med Chem. 5 (8): 761–78. PMID 16101412.</ref> VDR-ligands have also been shown to affect maturation, differentiation, and migration of dendritic cells. Together these effects inhibit DC-dependent T cell activation, resulting in an overall state of immunosuppression.<ref>van Etten E, Mathieu C. (2005). "Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts.". J Steroid Biochem Mol Biol. 97 (1-2): 93–101. PMID 16046118.</ref> VDR ligands have also been shown to enhance the phagocytic activity of macrophages, and to increase the activity of natural killer cells.<ref name= PDR/>

The immunoregulatory properties of the VDR indicate that ligands with the potential to activate the VDR, including supplementation with calcitriol (as well as a number of synthetic modulators), may have therapeutic clinical applications in the treatment of; inflammatory diseases (rheumatoid arthritis, psoriatic arthritis), dermatological conditions (psoriasis, actinic keratosis), osteoporosis, cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis) and in preventing Organ (anatomy) transplant rejection.<ref name= Endo/> However the effects of supplementation with vitamin D, as yet, remain unclear, and supplementation may be inadvisable for individuals with sarcoidosis and other diseases involving vitamin D hypersensitivity.<ref>United Kingdom Food Standards Agency; Expert Group on Vitamins and Minerals; Professor Michael Langdon, Chairman. (2003 May). Safe Upper Levels for Vitamins and Minerals. Retrieved Aug. 12, 2006 from http://www.food.gov.uk/multimedia/pdfs/vitmin2003.pdf</ref><ref>Vieth R (1999). "Full Text Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety". Am J Clin Nutr 69 (5): 842-56. PMID 10232622.</ref><ref name="Abreu">Abreu MT, et. al. (2004). "Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn’s disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density". Gut 53 (8): 1129-1136. PMID 15247180.</ref>

[edit] Role in cancer prevention and recovery

In 2005, scientists released a study which demonstrated a beneficial correlation between vitamin D intake and prevention of cancer.<ref>"Vitamin D 'can lower cancer risk'", BBC News, 28 December 2005. Retrieved on 2006-03-23.</ref> Drawing from their meta-analysis of 63 published reports, the scientists showed that an additional intake of 1,000 international units (IU) — or 25 micrograms — of the vitamin daily could lower an individual's risk of colon cancer by 50%, and risk of breast and ovarian cancer by 30%. These are cross-sectional data, and thus the evidence is circumstantial. Longitudinal trials would be able to provide more conclusive proof of vitamin D's ability to prevent cancer.

Research suggests that cancer patients who have their surgery or treatment in the summer — and therefore get more vitamin D — have a better chance of surviving than those who undergo treatment in the winter when they are exposed to less sunlight.<ref>"Vitamin D 'aids lung cancer ops'", BBC News, 22 April 2005. Retrieved on 2006-03-23.</ref>

[edit] Notes and references

<references/>

[edit] External links


Vitamins
Retinol (A) | B vitamins (Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenic acid (B5), Pyridoxine (B6), Biotin (B7), Folic acid (B9), Cyanocobalamin (B12)) | Choline | Ascorbic acid (C) | Ergocalciferol and Cholecalciferol (D) | Tocopherol (E) | Naphthoquinone (K)
Hormones and endocrine glands - edit

Hypothalamus: - TRH - CRH - GnRH - GHRH - somatostatin - dopamine | Posterior pituitary: vasopressin - oxytocin - lipotropin | Anterior pituitary: GH - ACTH - TSH - LH - FSH - prolactin - MSH - endorphins - lipotropin

Thyroid: T3 and T4 - calcitonin | Parathyroid: PTH | Adrenal medulla: epinephrine - norepinephrine | Adrenal cortex: aldosterone - cortisol - DHEA | Pancreas: glucagon- insulin - somatostatin | Ovary: estradiol - progesterone - inhibin - activin | Testis: testosterone - AMH - inhibin | Pineal gland: melatonin | Kidney: renin - EPO - calcitriol - prostaglandin | Heart atrium: ANP

Stomach: gastrin | Duodenum: CCK - GIP - secretin - motilin - VIP | Ileum: enteroglucagon | Liver: IGF-1

Placenta: hCG - HPL - estrogen - progesterone

Adipose tissue: leptin, adiponectin

Target-derived NGF, BDNF, NT-3

ar:فيتامين دي

ca:Vitamina D cs:Kalciferol da:D-vitamin de:Calciferol et:D-vitamiin es:Vitamina D eo:Vitamino D fa:ویتامین د fr:Vitamine D ko:바이타민 D hr:Vitamin D it:Colecalciferolo he:ויטמין D lt:Vitaminas D nl:Vitamine D ja:ビタミンD no:Vitamin D pl:Witamina D pt:Vitamina D ru:Витамин D sk:Vitamín D sl:Vitamin D sh:Vitamin D fi:D-vitamiini tr:D vitamini uk:Вітамін D zh:維生素D

Retrieved from "http://en.wikivisual.com/index.php/Vitamin_D"
Personal tools